In 1993, We analyzed whole sequences of HBV DNA from an patient with fulminant hepatitis B.The result demonstrated that this viral DNA harbared 4,12,15 and 6 missense mutations in envelope, core, pol and X region, respectively.In 1994, in order to study the biological properties of the mutated HBV DNA from fulminant hepatitis B,we transfected the mutated HBV DNA constract into HepG2 cells and checked viral protein in culture medium and viral replication inside the hepatoma cells. As a result, this HBV DNA showed high level of production of HBV core protein and replicative intermediate.In 1995, in order to study how this mutant virus worked in vivo, we established murine hepatitis model, in which viral protein was secreted into circulation and expressed in hepatocytes. We injected the mixture of HBV DNA constract and lipofectin under the capsule of the murine liver. Serial analysis demonstrated that HBsAg was detected in circulation followed by the seroconversion from HBsAg to anti-HBs in circulation and HBsAg and HBcAg was expressed in murine hepatocyte. The study for the establishment of murine fulminant hepatitis model is ongoing.